Vitamin and mineral supplements for human and veterinary use are commonplace. Some diets, heavy physical exercise and disease conditions may require the intake of considerable quantities of minerals and vitamins apart from those generally obtained through what otherwise would be considered a normal diet. Calcium and vitamin supplementation is important primarily for those who have inadequate diets, including growing children. Older adults have an additional need for calcium to help prevent the bone loss which occurs as a normal consequence of the aging process. In particular, postmenopausal women need additional calcium due to hormonal changes which can accelerate the bone loss rate leading to a further diminishment in bone mass.
There are well-recognized problems associated with adding both calcium and vitamin D to foods and beverages. Some of these are taste; calcium tends to be chalky in flavor. In addition, the solubility of many calcium sources prevents them from being added to many beverages. Interactions of calcium with the food or beverage affect the stability and/or the bioavailabilty of the product. This invention provides a means for making such product.
This invention also relates to methods of building bone in humans and other animals, i.e., for the treatment of age-related bone loss and related disorders. In particular, this invention relates to such methods of treatment by administration of calcium, citrate and malate ions and vitamin D.
Calcium is the fifth most abundant element in the human body. It plays an important role in many physiological processes, including nerve and muscle functions. Not surprisingly, nutritional and metabolic deficiencies of calcium can have broad-ranging adverse effects. Since about 98% to 99% of the body's calcium is found in bone tissues, many of these adverse effects are manifested through deficiencies in the structure, function and integrity of the skeletal system.
The most common metabolic bone disorder is osteoporosis. Osteoporosis can be generally defined as the reduction in the quantity of bone, either from the reduction in bone formation or the acceleration of bone resorption, in either event the result is a decrease in the amount of skeletal tissue and resultant bone fractures. In general, there are two types of osteoporosis: primary and secondary. "Secondary osteoporosis" is the result of an identifiable disease process or agent. However, approximately 90% of all osteoporosis cases are idiopathic "primary osteoporosis". Such primary osteoporosis includes postmenopausal osteoporosis, age-associated osteoporosis (affecting a majority of individuals over the age of 70 to 80), and idiopathic osteoporosis affecting middle-aged and younger men and women.
For some osteoporotic individuals the loss of bone tissue is sufficiently great so as to cause mechanical failure of the bone structure. Bone fractures often occur, for example, in the wrist, hip and spine of women suffering from postmenopausal osteoporosis. Kyphosis (abnormally increased curvature of the thoracic spine) may also result.
The mechanism of bone loss in osteoporotics is believed to involve an imbalance in the process of "bone remodeling". Bone remodeling occurs throughout life, renewing the skeleton and maintaining the strength of bone. Two reactions are involved, bone loss or resorption and bone growth or accretion. This remodeling occurs in a series of discrete pockets of activity in the bone. These pockets are lined with two different cell types called "osteoclasts" and "osteoblasts". Osteoclasts (bone dissolving or resorbing cells) are responsible for the resorption of a portion of bone within the bone matrix, during the resorption process. After resorption, the osteoclasts are followed by the appearance of osteoblasts (bone forming cells), which then refill the resorbed portion with new bone.
In young healthy adults, the rate at which the osteoclasts and osteoblasts are formed maintains a balance of bone resorption and bone formation. However, as a normal consequence of aging an imbalance in this remodeling process develops, resulting in loss of bone at a rate faster than the accretion of bone. As imbalance continues over time the reduction in bone mass and thus bone strength leads to fractures.
Many compositions and methods are described in the medical literature for the "treatment" of osteoporosis. See, for example, R. C. Haynes, Jr. et al., "Agents affecting Calcification", The Pharmacological Basis of Therapeutics, 7th Edition (A. G. Gilman, L. S. Goodman et al., Editors, 1985); and G. D. Whedon et al., "An Analysis of Current Concepts and Research Interest in Osteoporosis", Current Advances in Skeletogenesis (A. Ornoy et al., Editors, 1985). Estrogen is often used to affect the metabolism of calcium by influencing the osteoblast cells. Treatments using fluoride have also been described. However, the utility of such agents may be limited, because of possible adverse side effects. See W. A. Peck, et al., Physician's Resource Manual on Osteoporosis (1987), published by the National Osteoporosis Foundation.
Nutritional therapies for osteoporosis have also been proposed. Many calcium-containing compounds and vitamins compositions have been described for use as nutritional supplements. Many commercial preparations are also available, typically containing calcium carbonate or calcium phosphate. Other calcium salts have also been described for use in calcium supplements, including calcium lactate, calcium citrate and calcium gluconate.
U.S. Pat. No. 3,949,098 issued Bangert (assigned Nabisco, 1976) describes a nutritious orange drink concentrate that contains whey protein. The patent suggests the addition of minor amounts of vitamins, including vitamin D, and other nutrients which include various minerals, such as calcium salts.
U.S. Pat. No. 4,497,800 issued to Larsen et al (assigned Mead Johnson & Company, 1985) describes a nutritionally complete ready-to-use liquid diet for providing total patient nourishment. The diet contains free amino acids and small peptides, a carbohydrate source, and nutritionally significant amounts of all essential vitamins and minerals, and stabilizers. Most of these minerals are given as the gluconate salt. Cholecalciferol (D.sub.3) is included.
"Effects of calcium carbonate in hydroxyapatite on zinc and iron retention in postmenopausal women", Dawson-Hughes, Seligson and Hughes, American Journal of Clinical Nutrition, 44, 83-88 (1986) describes the effect of calcium carbonate on whole-body retention of zinc and iron in thirteen healthy post menopausal women. The test meal, including both dry food and a formulated beverage, included iron, calcium, copper and zinc at a level of one-third the usual daily requirement. These are levels normally found in human diets.
U.S. Pat. No. 3,992,555 issued to Kovacs (assigned Vitamins, Inc., 1976) describes food supplements prepared by mixing assimilable iron compounds, vitamins and minerals with a heated edible fat carrier. Calcium and vitamin D are among the minerals in the supplement.
U.S. Pat. No. 3,950,547 issued to Lamar et al (assigned Syntex Inc, 1976) describes a dietary composition containing peptides and/or amino acids, lipids and carbohydrates in an aqueous emulsion. Vitamins, including D, are added. Calcium citrate is also used.
U.S. Pat. No. 4,070,488 issued to Davis (unassigned, 1978) discloses a highly stabilized balanced nutritive composition useful in supplementing the diet of humans and/or animals. This composition contains gelatin. The patent discloses that the sulfhydryl groups of the gelatin can render copper inactive toward ascorbic acid.
U.S. Pat. No. 4,214,996 issued to Buddemeyer et al (R.G.B. Laboratories, 1980) discloses mineral compositions which are very soluble. These compositions contain calcium, other minerals and vitamins.
U.S. Pat. No. 4,351,735 to Buddemeyer et al (R.G.B. Laboratories, 1982) is related to the '996 patent.
"Nutrients and Nutrition of Citrus Fruits," Citrus Nutrition and Quality, Ting, (American Chemical Society, 1980) discloses the presence of certain trace minerals in orange juice. Calcium and magnesium are the two major divalent cations in orange juice. The levels of all the minerals are low. No vitamin D has been reported in citrus juices.
Milk contains solubilized calcium and is often fortified with vitamin D. Milk's calcium is about 50% calcium citrate and 50% calcium phosphoprotein complexes.
The utility of these known supplements varies. Unlike agents (such as estrogen) which affect the metabolism of bone, calcium nutritional supplements have been thought to merely provide a source for calcium (which may or may not be properly absorbed and metabolized). See, for example, B. Riis et al., "Does Calcium Supplementation Prevent Postmenopausal Bone Loss?," New England J. of Medicine, 316, 173-177 (1987); L. Nilas et al., "Calcium Supplementation and Postmenopausal Bone Loss," British Medical Journal, 289, 1103-1106 (1984); and H. Spencer et al., "NIH Concensus Conference: Osteoporosis," Journal of Nutrition, 116, 316-319 (1986).
It has now been discovered, however, that the administration of mixtures of certain calcium salts, i.e. calcium citrate and malate, and vitamin D are effective for delaying age-related loss of bone. In particular, as compared to nutritional regimens known in the art, these methods afford greater efficacy in the treatment of age-related bone loss and related disorders.
It would be desirable, therefore, to have mixed calcium and vitamin D therapies which are compatible and nutritionally available. It would also be quite useful to have such supplements which could be added to food and beverage compositions without undesirably affecting organoleptic or aesthetic properties.
It is an object of the present invention to provide calcium mineral supplements which, when combined with vitamin D, provide bone growth and can be used to treat age-related bone loss or to correct the imbalance that occurs between bone formation and bone resorption.
It is a further object of this invention to provide foodstuffs, beverages and beverage concentrates which are supplemented with calcium and vitamin D therapies.
These and other objects are readily apparent from the description herein.